LATS1 K751 acetylation blocks activation of Hippo signalling and switches LATS1 from a tumor suppressor to an oncoprotein.
Sci China Life Sci
; 65(1): 129-141, 2022 01.
Article
in En
| MEDLINE
| ID: mdl-33945069
ABSTRACT
Large tumor suppressor 1 (LATS1) is the key kinase controlling activation of Hippo signalling pathway. Post-translational modifications of LATS1 modulate its kinase activity. However, detailed mechanism underlying LATS1 stability and activation remains elusive. Here we report that LATS1 is acetylated by acetyltransferase CBP at K751 and is deacetylated by deacetylases SIRT3 and SIRT4. Acetylation at K751 stabilized LATS1 by decreasing LATS1 ubiquitination and inhibited LATS1 activation by reducing its phosphorylation. Mechanistically, LATS1 acetylation resulted in inhibition of YAP phosphorylation and degradation, leading to increased YAP nucleus translocation and promoted target gene expression. Functionally, LATS1-K751Q, the acetylation mimic mutant potentiated lung cancer cell migration, invasion and tumor growth, whereas LATS1-K751R, the acetylation deficient mutant inhibited these functions. Taken together, we demonstrated a previously unidentified post-translational modification of LATS1 that converts LATS1 from a tumor suppressor to a tumor promoter by suppression of Hippo signalling through acetylation of LATS1.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Acetylation
/
Protein Serine-Threonine Kinases
/
Tumor Suppressor Proteins
/
Hippo Signaling Pathway
Limits:
Animals
Language:
En
Journal:
Sci China Life Sci
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2022
Document type:
Article
Affiliation country:
China